Endoglin, also known as CD105, is a homodimeric cell membrane glycoprotein that is predominantly expressed on endothelial cells such as syncytiotrophoblasts, human umbilical vein endothelial cells (HUVEC), and on vascular endothelial cells. Endoglin shares sequence identity with betaglycan, a transforming growth factor (TGF)-β receptor type III. Endoglin has been shown to be a regulatory component of the TGF-β receptor complex, which modulates angiogenesis, proliferation, differentiation, and apoptosis. Endoglin also binds several other members of the TGF-β superfamily including activin-A, bone morphogenic protein (BMP)-2, and BMP-7. In particular, endoglin binds TGF-β1 and TGF-β3 with high affinity and forms heterotrimeric associations with the TGF-β signaling receptors types I and II. Mutations in the coding region of the endoglin gene are responsible for haemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage.
A soluble form of endoglin was previously identified and found to interfere with TGF-β1 signaling and endothelial nitric oxide synthase (eNOS) activation in endothelial cells, thereby disrupting mechanisms necessary for maintenance of vascular health. Soluble endoglin was found to be present at increased levels in patients with metastatic breast and colorectal cancer. It has also been shown that patients having pre-eclampsia produce large quantities of soluble endoglin and that soluble endoglin contributes to the pathogenesis of pre-eclampsia.
There is a need for methods of treating and diagnosing subjects at risk for or having a soluble endoglin-mediated disorder (e.g., eclampsia and pre-eclampsia) or a soluble endoglin-preventive disorder (e.g., disorders characterized by increased TGF β expression or biological activity).